The present invention relates to recombinant human fibrin sealant (rhFS), which comprises recombinant human fibrinogen (rhFbgn), recombinant human thrombin (rhThrombin) and optionally recombinant human FXIII.
Fibrin sealant (FS) is a mixture of three protein components: Fibrinogen (Fbgn), Thrombin, and Factor XIII (FXIII). Fbgn forms the structural matrix of the sealant and is present in the largest concentration. Thrombin and FXIII are enzymes, and are present in much lower concentrations. Existing FS are prepared using Fbgn purified from human blood, and thrombin purified from either bovine or human sources. The Fbgn for commercial FS is derived from pooled plasma, but Fbgn for FS is also purified from single-donor and autologous sources by many blood banks. Regardless of the source of the components, FS are typically formulated as two solutions: Fbgn+FXIII, and Thrombin+CaCl2. When mixed, the thrombin converts Fbgn to fibrin (Fbn), and polymerises to form a gel. Thrombin also converts the zymogen (inactive) form of FXIII to the active form that, in the presence of calcium, covalently cross-links the polymerised Fbn molecules to strengthen the gel and modify its physical properties (FIG. 1). When Fbgn is purified from human plasma, the FXIII is normally co-purified as a contaminant of the Fbgn. (FS prepared from blood-derived Fbgn may also contain other proteins, such as fibronectin (FN) and growth factors, as contaminants.)
The present invention provides a totally recombinant Fibrin Sealant (rhFS), which comprises recombinant human Fbgn (rhFbgn), recombinant human thrombin (rhThrombin) and optionally recombinant human FXIII (rhFXIII) (zymogen or active). Recombinant human fibrin sealant (rhFS) is an alternative to existing fibrin sealants (FS) derived from non-recombinant components.